Department of Endocrinology and Metabolism, University of Amsterdam, Amsterdam, Netherlands

Department of Neurosciences, University of California, San Diego, La Jolla , CA, USA

Circulating triglycerides (TG) normally increase after a
meal but are altered in pathophysiological conditions such as obesity. Although TG metabolism in the brain remains
poorly understood, several brain structures express enzymes that process
TG-enriched particles, including mesolimbic structures. For this reason, and because consumption of
high fat diet alters dopamine signalling, we tested the hypothesis that TG
might directly target mesolimbic reward circuits to control reward-seeking
behaviors. We found that the delivery of
small amounts of TG to the brain through the carotid artery rapidly reduced
both spontaneous and amphetamine-induced locomotion, abolished preference for
palatable food, and reduced the motivation to engage in food-seeking behavior.
Conversely, targeted disruption of the TG-hydrolyzing enzyme lipoprotein lipase
specifically in the nucleus accumbens increased palatable food preference and
food seeking behavior. Finally, prolonged TG perfusion resulted in a return to
normal palatable food preference despite continued locomotor suppression,
suggesting that adaptive mechanisms occur. These findings reveal new mechanisms
by which dietary fat may alter mesolimbic circuit function and reward
seeking.